Pathways to Alcohol Use Disorders in ALSPAC: A Genetic-Developmental Study Alcohol Use Disorders (AUDs) emerge from diverse genetic and environmental risk factors acting through a range of complex developmental pathways. Very few studies exist that have a combination of sample size, representativeness, and sufficiently frequent and detailed assessments over the requisite age range to provide a realistic opportunity to disentangle these intricate etiologic pathways. The Avon Longitudinal Study of Parents and Children (ALSPAC) is such a study. Beginning with over 13,000 pregnant mothers ascertained around Avon England, the ALSPAC project has conducted detailed follow-ups of this sample for the last 16 years. The sample is now entering the critical transitional period from adolescence to young adulthood. This application, prepared by a team of investigators from Virginia Commonwealth University and University of Bristol, has three specific aims in the ALSPAC cohort. The first aim is to add detailed assessments of alcohol use and symptoms of AUDs to questionnaires already scheduled to occur at ages 18 and 20. This will allow us to capture a key developmental phase for alcohol use and the emergence of early symptoms of AUDs. The second aim is to conduct an extensive series of analyses seeking to understand the etiologic pathways to alcohol use (AU) and alcohol use problems (AUPs). The specific goals of these analyses will be (1) to characterize patterns of AU and AUPs across adolescence;(2) to identify childhood risk factors that predict AU and AUPs in adolescence and to understand the developmental processes by which these risks unfold;(3) to study the further development of these risk factors across adolescence and their interaction with emerging AU and its consequences;(4) to test the moderating role of gender on patterns, predictors, and developmental processes related to AU and AUPs;and (5) to extend models of risk for AU and AUPs into young adulthood using the age 18 and 20 data collected under Aim 1. The analyses will examine how risk unfolds across development across three major domains: Externalizing, Internalizing, and Environment (and how these eventually relate to AU and the development of AUPs). Each of these domains is broad, and one of the goals of the project will be to parse these constructs and delineate the most relevant risk dimensions. The third aim of the project is to incorporate information about a limited set of previously validated risk genes into developmental models of risk for AU, AUPs, and AUDs developed in Aim 2. This will be accomplished using molecular genetic data available on at least 3,000 subjects from the ALSPAC cohort at no cost to NIH. These analyses will allow us to study the dynamic interplay of biological, psychological, and social processes that contribute to pathways of risk (and resiliency) for AU and AUPs. With its large sample size, representativeness, detailed and frequent phenotypic assessments and availability of genotypic data, the ALSPAC cohort provides a unique opportunity to clarify, in a developmental context, the complex web of susceptibility and protective factors for AUDs.